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Cancers Jun 2024Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms....
Gliomas are primary brain lesions involving cerebral structures without well-defined boundaries and constitute the most prevalent central nervous system (CNS) neoplasms. Among gliomas, glioblastoma (GB) is a glioma of the highest grade and is associated with a grim prognosis. We examined how clinical variables and molecular profiles may have affected overall survival (OS) over the past ten years. A retrospective study was conducted at Sina Hospital in Tehran, Iran and examined patients with confirmed glioma diagnoses between 2012 and 2020. We evaluated the correlation between OS in GB patients and sociodemographic as well as clinical factors and molecular profiling based on IDH1, O-6-Methylguanine-DNA Methyltransferase (MGMT), TERTp, and epidermal growth factor receptor (EGFR) amplification (EGFR-amp) status. Kaplan-Meier and multivariate Cox regression models were used to assess patient survival. A total of 178 patients were enrolled in the study. The median OS was 20 months, with a 2-year survival rate of 61.0%. Among the 127 patients with available IDH measurements, 100 (78.7%) exhibited mutated IDH1 (IDH1-mut) tumors. Of the 127 patients with assessed MGMT promoter methylation (MGMTp-met), 89 (70.1%) had MGMT methylated tumors. Mutant TERTp (TERTp-mut) was detected in 20 out of 127 cases (15.7%), while wildtype TERTp (wildtype TERTp-wt) was observed in 107 cases (84.3%). Analyses using multivariable models revealed that age at histological grade ( < 0.0001), adjuvant radiotherapy ( < 0.018), IDH1 status ( < 0.043), and TERT-p status ( < 0.014) were independently associated with OS. Our study demonstrates that patients with higher tumor histological grades who had received adjuvant radiotherapy exhibited IDH1-mut or presented with TERTp-wt experienced improved OS. Besides, an interesting finding showed an association between methylation of MGMTp and TERTp status with tumor location.
PubMed: 38893240
DOI: 10.3390/cancers16112121 -
Nutrients Jun 2024NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this...
NASH (non-alcoholic steatohepatitis) is a severe liver disease characterized by hepatic chronic inflammation that can be associated with the gut microbiota. In this study, we explored the therapeutic effect of extract (GPE), a Chinese herbal extract, on methionine- and choline-deficient (MCD) diet-induced NASH mice. Based on the peak area, the top ten compounds in GPE were hydroxylinolenic acid, rutin, hydroxylinoleic acid, vanillic acid, methyl vanillate, quercetin, pheophorbide A, protocatechuic acid, aurantiamide acetate, and iso-rhamnetin. We found that four weeks of GPE treatment alleviated hepatic confluent zone inflammation, hepatocyte lipid accumulation, and lipid peroxidation in the mouse model. According to the 16S rRNA gene V3-V4 region sequencing of the colonic contents, the gut microbiota structure of the mice was significantly changed after GPE supplementation. Especially, GPE enriched the abundance of potentially beneficial bacteria such as and decreased the abundance of opportunistic pathogens such as . Moreover, RNA sequencing revealed that the GPE group showed an anti-inflammatory liver characterized by the repression of the NF-kappa B signaling pathway compared with the MCD group. Ingenuity Pathway Analysis (IPA) also showed that GPE downregulated the pathogen-induced cytokine storm pathway, which was associated with inflammation. A high dose of GPE (HGPE) significantly downregulated the expression levels of the tumor necrosis factor-α (TNF-α), myeloid differentiation factor 88 (Myd88), cluster of differentiation 14 (CD14), and Toll-like receptor 4 (TLR4) genes, as verified by real-time quantitative PCR (RT-qPCR). Our results suggested that the therapeutic potential of GPE for NASH mice may be related to improvements in the intestinal microenvironment and a reduction in liver inflammation.
Topics: Animals; Gastrointestinal Microbiome; Non-alcoholic Fatty Liver Disease; Mice; Gynostemma; Plant Extracts; Male; Inflammation; Liver; Mice, Inbred C57BL; Disease Models, Animal; Signal Transduction; Anti-Inflammatory Agents
PubMed: 38892715
DOI: 10.3390/nu16111782 -
Nutrients May 2024Aging and its related disorders are important issues nowadays and the first cause of this physio-pathological condition is the overproduction of ROS. Ascorbic acid is an...
Aging and its related disorders are important issues nowadays and the first cause of this physio-pathological condition is the overproduction of ROS. Ascorbic acid is an antioxidant mediator and its anti-aging proprieties are well known. Our previous data demonstrated that Voghera sweet pepper (VP), a distinctive type of pepper cultivated in Italy, is particularly rich in ascorbic acid. Based on these data, the anti-aging effect mediated by extracts of the edible part of VP was evaluated on an in vitro model of both young and old Normal Human Diploid Fibroblasts (NHDF). Using phase contrast microscopy, we observed that VP may help cells in the maintenance of physiological morphology during aging. Cytofluorimetric analyses revealed that VP extracts led to an increase in DNA synthesis and percentage of living cells, linked to a consequent increase in mitotic events. This hypothesis is supported by the enhancement of PCNA expression levels observed in old, treated fibroblasts, corroborating the idea that this extract could recover a young phenotype in adult fibroblasts, confirmed by the study of p16 and p53 expression levels and TEM analyses. Based on these results, we may suppose that VP can lead to the partial recovery of "young-like" phenotypes in old fibroblasts.
Topics: Humans; Fibroblasts; Capsicum; Cellular Senescence; Plant Extracts; Cell Proliferation; Ascorbic Acid; Tumor Suppressor Protein p53; Proliferating Cell Nuclear Antigen; Cyclin-Dependent Kinase Inhibitor p16; Aging; Antioxidants; Diploidy; Cells, Cultured; Italy
PubMed: 38892614
DOI: 10.3390/nu16111681 -
International Journal of Molecular... Jun 2024Spontaneous tumour formation in higher plants can occur in the absence of pathogen invasion, depending on the plant genotype. Spontaneous tumour formation on the...
Spontaneous tumour formation in higher plants can occur in the absence of pathogen invasion, depending on the plant genotype. Spontaneous tumour formation on the taproots is consistently observed in certain inbred lines of radish ( var. Pers.). In this paper, using Oxford Nanopore and Illumina technologies, we have sequenced the genomes of two closely related radish inbred lines that differ in their ability to spontaneously form tumours. We identified a large number of single nucleotide variants (amino acid substitutions, insertions or deletions, SNVs) that are likely to be associated with the spontaneous tumour formation. Among the genes involved in the trait, we have identified those that regulate the cell cycle, meristem activity, gene expression, and metabolism and signalling of phytohormones. After identifying the SNVs, we performed Sanger sequencing of amplicons corresponding to SNV-containing regions to validate our results. We then checked for the presence of SNVs in other tumour lines of the radish genetic collection and found the gene, which had the SNVs in the majority of tumour lines. Furthermore, we performed the identification of the () and () genes and, as a result, identified two unique radish genes which probably encode proteins with multiple CLE domains. The results obtained provide a basis for investigating the mechanisms of plant tumour formation and also for future genetic and genomic studies of radish.
Topics: Raphanus; Whole Genome Sequencing; Genome, Plant; Plant Tumors; Polymorphism, Single Nucleotide; Plant Proteins
PubMed: 38892425
DOI: 10.3390/ijms25116236 -
International Journal of Molecular... Jun 2024Blackberries (), which are known to include a variety of bioactive substances, have been extensively studied for their antioxidant properties. Blackberries possess...
Blackberries (), which are known to include a variety of bioactive substances, have been extensively studied for their antioxidant properties. Blackberries possess multiple health beneficial effects, including anti-inflammation, anti-atherosclerosis, anti-tumor and immunomodulatory activity. However, the potential biological effects and precise molecular mechanisms of the fermented extracts remain largely unexplored. In this research, we demonstrate the effect of blackberries fermented with for addressing obesity. We investigated the effect of blackberries fermented by on mice fed a high-fat (60% kcal) diet for 12 weeks. Fermented blackberry administration reduced the body weight and epididymal fat caused by a high-fat diet compared to the obese group. The triglyceride and total cholesterol, which are blood lipid indicators, and the levels of leptin, which is an insulin resistance indicator, were significantly increased in the obese group but were significantly decreased in the fermented blackberries-treated group. Additionally, the expression of adipogenesis marker proteins, such as CEBPα, PPAR-γ and SREBP-1, was significantly increased in the obese group, whereas it was decreased in the fermented blackberries-treated group. These results suggest that fermented blackberries have a protective effect against high-fat-diet-induced obesity by inhibiting adipogenesis and are a potential candidate for the treatment of obesity.
Topics: Animals; Adipogenesis; Rubus; Mice; Obesity; Anti-Obesity Agents; Male; Diet, High-Fat; PPAR gamma; Fermentation; Signal Transduction; Lactobacillus plantarum; Plant Extracts; Sterol Regulatory Element Binding Protein 1; Mice, Inbred C57BL; Leptin; CCAAT-Enhancer-Binding Proteins; Triglycerides; Body Weight
PubMed: 38892352
DOI: 10.3390/ijms25116164 -
International Journal of Molecular... Jun 2024Carnivorous pitcher plants from the genus are renowned for their ethnobotanical uses. This research explores the therapeutic potential of leaf extract against...
Inhibition of SARS-CoV-2 Nsp9 ssDNA-Binding Activity and Cytotoxic Effects on H838, H1975, and A549 Human Non-Small Cell Lung Cancer Cells: Exploring the Potential of Leaf Extract for Pulmonary Disease Treatment.
Carnivorous pitcher plants from the genus are renowned for their ethnobotanical uses. This research explores the therapeutic potential of leaf extract against nonstructural protein 9 (Nsp9) of SARS-CoV-2 and in treating human non-small cell lung carcinoma (NSCLC) cell lines. Nsp9, essential for SARS-CoV-2 RNA replication, was expressed and purified, and its interaction with ssDNA was assessed. Initial tests with myricetin and oridonin, known for targeting ssDNA-binding proteins and Nsp9, respectively, did not inhibit the ssDNA-binding activity of Nsp9. Subsequent screenings of various extracts identified those using acetone, methanol, and ethanol as particularly effective in disrupting Nsp9's ssDNA-binding activity, as evidenced by electrophoretic mobility shift assays. Molecular docking studies highlighted stigmast-5-en-3-ol and lupenone, major components in the leaf extract of , as potential inhibitors. The cytotoxic properties of leaf extract were examined across NSCLC lines H1975, A549, and H838, focusing on cell survival, apoptosis, and migration. Results showed a dose-dependent cytotoxic effect in the following order: H1975 > A549 > H838 cells, indicating specificity. Enhanced anticancer effects were observed when the extract was combined with afatinib, suggesting synergistic interactions. Flow cytometry indicated that leaf extract could induce G2 cell cycle arrest in H1975 cells, potentially inhibiting cancer cell proliferation. Gas chromatography-mass spectrometry (GC-MS) enabled the tentative identification of the 19 most abundant compounds in the leaf extract of . These outcomes underscore the dual utility of leaf extract in potentially managing SARS-CoV-2 infection through Nsp9 inhibition and offering anticancer benefits against lung carcinoma. These results significantly broaden the potential medical applications of leaf extract, suggesting its use not only in traditional remedies but also as a prospective treatment for pulmonary diseases. Overall, our findings position the leaf extract of as a promising source of natural compounds for anticancer therapeutics and antiviral therapies, warranting further investigation into its molecular mechanisms and potential clinical applications.
Topics: Humans; Plant Extracts; Carcinoma, Non-Small-Cell Lung; SARS-CoV-2; Plant Leaves; Lung Neoplasms; Molecular Docking Simulation; Cell Line, Tumor; Viral Nonstructural Proteins; A549 Cells; COVID-19 Drug Treatment; COVID-19; Apoptosis; Antiviral Agents
PubMed: 38892307
DOI: 10.3390/ijms25116120 -
International Journal of Molecular... May 2024Hook. & Arn (Asteraceae), commonly known as Vautro, is found in the coastal areas of central-southern Chile, including the industrial zone of Quintero-Puchuncaví,...
Hook. & Arn (Asteraceae), commonly known as Vautro, is found in the coastal areas of central-southern Chile, including the industrial zone of Quintero-Puchuncaví, known for the contamination of its soils with heavy metals, which together with other factors generate abiotic stress in plant species, against which they present defensive mechanisms. For this reason, the objective was to evaluate the effect of abiotic stress generated by the proximity of to the industrial complex by assessing the physiological and metabolic states reported by the extracts and compounds isolated from the species, as well as the photosynthetic capacity, metal content and production, and antioxidant activity and cytotoxicity against tumorigenic cell lines of the phytoconstituents. To this end, was collected at two different distances from the industrial complex, observing that the closer the species is, the greater the concentration of copper in the soil, generating a decrease in the rate of electron transport in situ, but an increase in antioxidant activity with low cytotoxicity. This activity could be due to the presence of flavonoids such as Hispidulin, Cirsimaritina, and Isokaempferida, as well as monoterpenes, oxygenated and non-oxygenated sesquiterpenes identified in this study.
Topics: Antioxidants; Baccharis; Humans; Plant Extracts; Cell Line, Tumor; Chile; Photosynthesis; Antineoplastic Agents, Phytogenic
PubMed: 38892183
DOI: 10.3390/ijms25115993 -
International Journal of Molecular... May 2024The circadian clock regulates biological cycles across species and is crucial for physiological activities and biochemical reactions, including cancer onset and... (Review)
Review
The circadian clock regulates biological cycles across species and is crucial for physiological activities and biochemical reactions, including cancer onset and development. The interplay between the circadian rhythm and cancer involves regulating cell division, DNA repair, immune function, hormonal balance, and the potential for chronotherapy. This highlights the importance of maintaining a healthy circadian rhythm for cancer prevention and treatment. This article investigates the complex relationship between the circadian rhythm and cancer, exploring how disruptions to the internal clock may contribute to tumorigenesis and influence cancer progression. Numerous databases are utilized to conduct searches for articles, such as NCBI, MEDLINE, and Scopus. The keywords used throughout the academic archives are "circadian rhythm", "cancer", and "circadian clock". Maintaining a healthy circadian cycle involves prioritizing healthy sleep habits and minimizing disruptions, such as consistent sleep schedules, reduced artificial light exposure, and meal timing adjustments. Dysregulation of the circadian clock gene and cell cycle can cause tumor growth, leading to the need to regulate the circadian cycle for better treatment outcomes. The circadian clock components significantly impact cellular responses to DNA damage, influencing cancer development. Understanding the circadian rhythm's role in tumor diseases and their therapeutic targets is essential for treating and preventing cancer. Disruptions to the circadian rhythm can promote abnormal cell development and tumor metastasis, potentially due to immune system imbalances and hormonal fluctuations.
Topics: Humans; Neoplasms; Circadian Rhythm; Animals; Circadian Clocks
PubMed: 38892035
DOI: 10.3390/ijms25115846 -
International Journal of Molecular... May 2024Piperine, an active plant alkaloid from black pepper ), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which...
Piperine, an active plant alkaloid from black pepper ), has several pharmacological effects, namely antioxidant, anti-inflammatory and immunomodulatory effects, which involve inhibiting molecular events associated with various stages of cancer development. The aim of this study was to investigate the molecular mechanisms of action of piperine in relation to its potential anticancer effect on head and neck cancer cells. Parameters related to neoplastic potential and cytokine, protein and gene expression were investigated in head and neck cancer cell lines (HEp-2 and SCC-25) treated with piperine. The results of the tests indicated that piperine modified morphology and inhibited viability and the formation of cell colonies. Piperine promoted genotoxicity by triggering apoptosis and cell cycle arrest in the G2/M and S phases. A decrease in cell migration was also observed, and there was decreased expression of MMP2/9 genes. Piperine also reduced the expression of inflammatory molecules (PTGS2 and PTGER4), regulated the secretion of cytokines (IFN- and IL-8) and modulated the expression of ERK and p38. These results suggest that piperine exerts anticancer effects on tumor cells by regulating signaling pathways associated with head and neck cancer.
Topics: Polyunsaturated Alkamides; Benzodioxoles; Piperidines; Alkaloids; Humans; Cell Line, Tumor; Signal Transduction; Head and Neck Neoplasms; Inflammation; Apoptosis; Cell Movement; Gene Expression Regulation, Neoplastic; Cytokines; Cell Survival; Cell Proliferation
PubMed: 38891950
DOI: 10.3390/ijms25115762 -
International Journal of Molecular... May 2024× , belonging to the genus of the Taxaceae family, is a unique hybrid plant derived from a natural crossbreeding between and . This distinctive hybrid variety... (Review)
Review
× , belonging to the genus of the Taxaceae family, is a unique hybrid plant derived from a natural crossbreeding between and . This distinctive hybrid variety inherits the superior traits of its parental species, exhibiting significant biological and medicinal values. This paper comprehensively analyzes from multiple dimensions, including its cultivation overview, chemical composition, and multifaceted applications in the medical field. In terms of chemical constituents, this study delves into the bioactive components abundant in and their pharmacological activities, highlighting the importance and value of these components, including paclitaxel, as the lead compounds in traditional medicine and modern drug development. Regarding its medicinal value, the article primarily discusses the potential applications of in combating tumors, antibacterial, anti-inflammatory, and antioxidant activities, and treating diabetes. By synthesizing clinical research and experimental data, the paper elucidates the potential and mechanisms of its primary active components in preventing and treating these diseases. In conclusion, demonstrates its unique value in biological research and tremendous potential in drug development.
Topics: Taxus; Humans; Chemistry, Pharmaceutical; Plant Extracts; Animals; Antioxidants
PubMed: 38891943
DOI: 10.3390/ijms25115756